title: Low-dose acetylsalicylic acid and gastrointestinal ulcers or bleeding--a cohort study of the effects of proton pump inhibitor use patterns.
abstract: OBJECTIVE
  The aim of this study was to investigate the associations between proton pump inhibitor (PPI) usage patterns and risk of severe gastrointestinal events in patients treated with low-dose acetylsalicylic acid (LDA).
  
  
  METHODS
  A nationwide cohort study in Sweden.
  
  
  METHODS
  All Swedish residents ≥ 40 years of age, without cancer and receiving LDA treatment (≥ 80% adherence for 365 days between 2005 and 2009) were identified in the Swedish Prescription Register. Continuous PPI use was defined as > 60 of 90 days covered by daily PPI doses and further divided into high (≥ 80%) or moderate (< 80) adherence. All other PPI use was defined as intermittent use.
  
  
  METHODS
  The risk of a combined end-point of gastrointestinal ulcer or bleeding was analysed using Cox proportional hazard models. We also investigated risk of > 45 days of LDA treatment interruption.
  
  
  RESULTS
  During a median follow-up of 2.5 years, 7880 of 648,807 (1.2%) LDA-treated patients experienced gastrointestinal events. In multivariable-adjusted models, both intermittent-PPI and no-PPI use were associated with increased risk of gastrointestinal ulcers or bleeding compared with continuous PPI use with a high level of adherence [hazard ratio (HR) 1.83 (95% CI 1.66-2.02) and 1.14 (95% CI 1.05-1.23), respectively]. Amongst continuous PPI users, moderate adherence also increased the risk of gastrointestinal ulcers or bleeding [HR 1.22 (95% CI 1.07-1.40)]. The risk of LDA treatment interruption was higher with intermittent PPI use [HR 1.16 (95% CI 1.14-1.19)] than continuous PPI use with high adherence.
  
  
  CONCLUSIONS
  In this large cohort of LDA users, intermittent PPI use was associated with higher risk of gastrointestinal ulcers or bleeding and interrupted LDA treatment, compared with continuous PPI use.
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Hedberg
authors.forename: J
authors.initials: J
authors.lastname: Sundström
authors.forename: M
authors.initials: M
authors.lastname: Thuresson
authors.forename: P
authors.initials: P
authors.lastname: Aarskog
authors.forename: J
authors.initials: J
authors.lastname: Oldgren
authors.forename: J
authors.initials: J
authors.lastname: Bodegard
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004363:Drug Utilization; D005260:Female; D005500:Follow-Up Studies; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010437:Peptic Ulcer / Q000139:chemically induced*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D013548:Sweden
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D001241:Aspirin
keywords: acetylsalicylic acid; medication adherence; peptic ulcer; prophylaxis; proton pump inhibitors